Genetic Variant NQO1:p.Ser263Cys (chr16-69711013-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000903.3(NQO1):c.788C>G(p.Ser263Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S263T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NQO1
NM_000903.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.25

Publications

0 publications found

Variant links:

Genes affected

NQO1 (HGNC:2874): (NAD(P)H quinone dehydrogenase 1) This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein's enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer's disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

NQO1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25265032).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000903.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NQO1	NM_000903.3	MANE Select	c.788C>G	p.Ser263Cys	missense	Exon 6 of 6	NP_000894.1	P15559-1
NQO1	NM_001025433.2		c.686C>G	p.Ser229Cys	missense	Exon 5 of 5	NP_001020604.1	P15559-2
NQO1	NM_001025434.2		c.674C>G	p.Ser225Cys	missense	Exon 5 of 5	NP_001020605.1	P15559-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NQO1	ENST00000320623.10	TSL:1 MANE Select	c.788C>G	p.Ser263Cys	missense	Exon 6 of 6	ENSP00000319788.5	P15559-1
NQO1	ENST00000564043.1	TSL:1	c.725C>G	p.Ser242Cys	missense	Exon 6 of 6	ENSP00000455020.1	H3BNV2
NQO1	ENST00000379047.7	TSL:1	c.686C>G	p.Ser229Cys	missense	Exon 5 of 5	ENSP00000368335.3	P15559-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251400

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.012

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

4.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

REVEL

Benign

0.066

Sift

Benign

0.079

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.28

MutPred

0.32

Loss of disorder (P = 0.0045)

MVP

0.60

MPC

0.77

ClinPred

0.79

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.34

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over